In the United States alone, approximately 500,000 deaths per year are due to ruptured vascular plaques that were considered insignificant by angiographic evaluations. Available screening and diagnostic methods are insufficient to identify possible victims before the event occurs. Therefore, there is a definite and urgent clinical need for a diagnostic imaging technique that can identify and characterize the vulnerability of atherosclerotic plaques during coronary artery interventions. The overall goal of our research program is to develop an in vivo imaging technology - combined intravascular ultrasound and photoacoustic imaging - capable of visualizing both structural properties and composition of atherosclerotic plaques. The underlying hypothesis of this project is that intravascular photoacoustic (IVPA) imaging combined with intravascular ultrasound (IVUS) imaging can be implemented clinically and used to detect and determine the vulnerability of atherosclerotic plaques. Therefore, combined IVUS/IVPA imaging can improve pre-intervention planning and assist with the intervention itself, thus improving the post-intervention outcome and reducing patient morbidity. Most importantly, the proposed IVUS/IVPA imaging will not significantly change the current clinical protocol of coronary artery intervention. A wide range of scientific, biomedical engineering, and clinical problems must be addressed to fully explore the capabilities of IVUS/IVPA imaging in interventional cardiology. The central theme of the current project is to develop and test a prototype of the combined IVUS/IVPA system for real-time in vivo imaging prior to extensive clinical studies. To achieve our objective, first we will design an build a prototype of the real-time in vivo IVUS/IVPA imaging system consisting of the custom-built IVUS/IVPA imaging catheters integrated with a motor assembly and interfaced with pulsed laser source, ultrasound transmitter/receiver, and microprocessor control unit. Second, we will develop the signal/image processing algorithms necessary to assess the anatomical features of the vessel wall and plaque to identify and quantify lipid-rich necrotic cores within atheroscleroti plaques. We will optimize the performance of the system hardware and signal/image processing algorithms by imaging ex vivo atherosclerotic arteries from animal models (rabbit and swine) and human coronary artery autopsy samples. Finally, the efficacy of the in vivo real-time IVUS/IVPA imaging system will be validated using live animal models of atherosclerosis. Based on the insights gathered during this project, we will be ready to perform further large animal and clinical studies to demonstrate that the IVUS/IVPA imaging system may become a superior clinical imaging tool needed in interventional cardiology.